Triggering receptor expressed on myeloid cells-1 is involved in microglia-induced inflammatory response after traumatic brain injury
Objective To investigate the regulatory mechanism of triggering receptor expressed on myeloid cells 1(Trem1)in inflammatory response after traumatic brain injury(TBI),and to provide theoreti-cal basis and intervention targets for reducing neuroinflammation and secondary injury.Methods Adult wild-type C57 male mice were divided into the sham group and the TBI group according to the random num-ber table method.The TBI model of mice was established by electronic controlled cortical impaction de-vice,with 6 mice in each group.The expression of Trem1 was detected by real-time fluorescent quantitative polymerase chain reaction(RT-qPCR),Western blotting and immunofluorescence.Wild-type C57 male mice were randomly divided into sham group and TBI group,and Trem1 knockout(Trem1-/-)male mice were randomly divided into sham group and TBI group,with 6 mice in each group.The protein expression of Trem1,interleukin(IL)-1β,IL-18,tumor necrosis factor-α(TNF-α),P-Syk,NLR family,pyrin do-main containing 3(NLRP3),cysteinyl aspartate-specific protease-1(Caspase-1)and ASC in the brain tis-sue was detected by Western blotting,and the brain water content was determined by dry-wet weight ratio.Wild type C57BL/6 male mice were randomly divided into the sham operation group,TBI group,and TBI+LR12(10 mg/kg)intervention group,with 6 mice in each group.The neurological function of each group was evaluated by modified neurological severity score and wire hang test.The t-test was used for comparison between the two groups,and one-way analysis of variance was used for comparison among groups.Results Compared with the sham group,Trem1 mRNA and protein levels were significantly in-creased at 3rd day after TBI(1.693±0.194 vs.1.015±0.072,t=5.666,P＜0.01;2.840±0.295 vs.1.033±0.134,t=8.618,P＜0.01).Immunofluorescence assay showed that Trem1 was not expressed in microglia in the sham group,and Trem1 was co-labeled with microglia in the TBI group.In wild-type mice,compared with the sham operation group,the relative protein expression levels of IL-1β,IL-18,TNF-α,p-Syk,NLRP3,Caspase-1 and ASC were significantly increased(2.623±0.412 vs.1.000±6.000,t=17.920,P＜0.01;1.640±0.195 vs.1.000±0.000,t=7.066,P＜0.01;2.307±0.284 vs.1.000±0.000,t=14.430,P＜0.01;2.163±0.206 vs.1.000±0.000,t=12.840,P＜0.01;2.820±0.282 vs.1.000±0.000,t=20.510,P＜0.01;1.923±0.132 vs.1.000±0.000,t=10.410,P＜0.01;2.170±0.149 vs.1.000±0.000,t=13.180,P＜0.01;1.823±0.134 vs.1.000±0.000,t=9.278,P＜0.01).Compared with the TBI group of wild type mice,the relative protein expression levels of IL-1β,IL-18,TNF-α,p-Syk,NLRP3,Caspase-1 and ASC in the TBI group of Trem1-/-mice were sig-nificantly decreased(1.287±0.065 vs.1.640±0.195,t=3.901,P＜0.05;1.897±0.122 vs.2.307±0.284,t=4.527,P＜0.05;1.760±0.104 vs.2.163±0.206,t=4.453,P＜0.05;1.513±0.263 vs.2.820±0.282,t=14.730,P＜0.01;1.503±0.156 vs.1.923±0.132,t=4.733,P＜0.05;1.593±0.194 vs.2.170±0.149,t=6.499,P＜0.01;1.420±0.171 vs.1.823±0.134,t=4.545,P＜0.05),and the brain water content was significantly decreased[(76.330±1.041)％vs.(81.330±1.756)％,t=4.549,P＜0.05].Compared with the sham group of wild type mice,the modified neurological severity score in the TBI group of wild type mice was significantly increased(10.500±1.517 vs.2.167±1.169,t=14.850,P＜0.01),and the time of holding the wire in the wire hang test was significantly reduced(51.000±9.899 vs.104.200±14.050,t=10.920,P＜0.01).Compared with the TBI group,the modi-fied neurological severity scores of the mice in the LR12 treatment group after TBI was significantly de-creased(8.000±1.414 vs.10.500±1.517,t=4.456,P＜0.05),and the holding time on the wire was significantly increased(73.830±11.440 vs.51.000±9.899,t=4.692,P＜0.05).Conclusion Trem1 is involved in microglia-induced neuroinflammation after TBI,and the use of inhibitors that specifically target Trem1 can improve neurological deficits after TBI.
Triggering receptor expressed on myeloid cells-1Traumatic brain injuryInflam-matory responseMicroglia
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